基于网络药理学的六味地黄丸治疗高血压、2型糖尿病、阿尔茨海默病的异病同治机制分析

Network Pharmacology Identifies the Mechanisms of LiuWei DiHuang Pill in the Treatment of Hypertension, Type 2 Diabetes and Alzheimer’s Disease

目的:借助网络药理学研究模式,以中医理论为指导原则,从分子水平探究六味地黄丸对高血压、2型糖尿病、阿尔茨海默病"异病同治"的物质基础和作用机制。方法:使用TCMSP、Swiss Target Prediction、STITCH数据库筛选出六味地黄丸的化学成分及其作用靶点,结合从Genecards、HPO、OMIM数据库以及GEO数据库中获取的基因芯片挖掘出的疾病靶点,将二者取交集后获取的共有靶点导入STRING数据库获得蛋白质相互作用关系,运用Cytoscape软件构建"中药-化合物-靶点"网络及PPI网络,运用Auto Dock软件进行分子对接。最后借助DAVID数据库进行GO和KEGG富集分析。结果:筛选出六味地黄丸活性成分69个,作用靶点280个,高血压、2型糖尿病、阿尔茨海默病及六味地黄丸共有靶点如VEGFA、IL-6、MMP-9、PPARG等21个。结论:该研究初步揭示了六味地黄丸对三病"异病同治"作用的现代生物学机制,包括影响血管生成及内皮功能、炎症反应、缺氧反应,为探究中医"异病同治"治疗原则的科学内涵提供了一定的依据。

Objective: This paper was to explore the common mechanisms of LiuWei DiHuang Pill(LWDH Pill) in treating Hypertension, Type 2 diabetes mellitus and Alzheimer’s disease under the guidance of traditional Chinese medicine theory based on network pharmacology. Methods: TCMSP, Swiss Target Prediction, STITCH databases were used to screen out the chemical components and its potential targets of LWDH Pill, then disease targets were obtained from Genecards, HPO and OMIM databases to achieve gene chip. By combining the two targets to obtain common targets and importing them into the STRING database, a protein interaction relationship was established and "Chinese medicine-compound-target" network and PPI network were constructed by Cytoscape software. Then we used Auto Dock software for molecular docking. Finally, DAVID database was used for GO and KEGG enrichment analysis. Results: 69 active ingredients and 280 targets were collected from LWDH Pill, 21 common targets including VEGFA、IL-6、MMP-9、PPARG from Hypertension, Type 2 diabetes mellitus, Alzheimer’s disease and LWDH Pill were screened out. Conclusion: This study preliminarily reveals the modern biological mechanism of LWDH Pill in treating three diseases, including angiogenesis and endothelial function, inflammatory reaction and hypoxia reaction. It provides a certain basis for exploring the scientific connotation of the principle of "treating different diseases with the same treatment" in traditional Chinese medicine.